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pTMB is a feasible predictive biomarker for chemoimmunotherapy

WCLC 2019
A biomarker which importance is clearly increasing, is the tumour mutational burden (TMB; number of somatic mutations per megabase [mut/Mb]). Furthermore, there has been some research into the role of plasma-based TMB as a biomarker, although this has been done only in anti-PD-L1 therapy studies or in combination therapy with PD-L1/cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade. Aggarwal et al. investigated whether pTMB can be used as a predictive biomarker in chemoimmunotherapy.

The researchers used a cohort which consisted of 66 treatment-naïve patients with stage IV non-squamous NSCLC without EGFR/ALK/ROS1/BRAF-mutations. Patients were randomised to pembrolizumab monotherapy (n=31) and pembrolizumab + chemotherapy (n=36). At 9 weeks, pTMB was compared to Response Evaluation Criteria in Solid Tumors (RECIST) response and 6 months durable clinical benefit. High and low pTMB were defined at a cut-off of 16 mut/Mb [1].

The results showed that median progression-free survival in patients with high pTMB was 13.8 vs 4.7 months in patients who had low pTMB (HR 0.27, 95% CI 0.13-0.55, P0.001). In patients with high pTMB, median overall survival was not achieved compared to 8.4 months in patients harbouring low pTMB (HR 0.47, 95% CI 0.20-1.10, P=0.083).

It was concluded that it is feasible to assess pTMB in patients who receive first-line treatment (which included chemoimmunotherapy) for advanced NSCLC. Mutations in STK11/KEAP1/PTEN as well as ERBB2 seem to be able to predict a lack of clinical benefit of immunotherapy. However, they agreed that the role of pTMB needs to be validated in larger, prospective studies.

  1. Aggarwal C, et al. MA25.04. WCLC 2019.

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